‘It is successful, and if it is successful, it reduces crime, and it can make the victims happier’: volunteers’ perceptions of working in restorative justice

Purpose: The purpose of the study was to explore the experiences of those volunteering within a Restorative Justice service thus enabling an insight into their perceptions of the different methods used, their beliefs about Restorative Justice effectiveness and its place within the Criminal Justice System (CJS). The study also sought to identify any challenges and positive experiences the participants encountered during their role as a volunteer, with volunteering during the COVID-19 pandemic explored specifically. Methodology: Data was collected from the participants (n=5) via semi-structured interviews and analysed using thematic analysis, thus enabling patterns within the experience of the volunteers to be identified. Findings: A prior understanding and interest in Restorative Justice was evident within the data, with participants demonstrating a preference for direct, face to face mediations. The perceived lack of support from external agencies was discussed along with the role of education in their volunteering experience. Finally, it was acknowledged that although face-to-face practice was deemed the most effective overall, certain practices adopted during Covid-19 enabled aspects of the role to be carried out more efficiently, and equally as effective. Practical implications: The findings from this study draw out real-world implications, producing tangible action points for Restorative Justice services. Some tentative suggestions for future practice are outlined. Originality: The volunteers’ role within Restorative Justice is often over-looked within the literature (Paul and Borton, 2013) and time constraints can add additional barriers to a hard-to-reach population. However, volunteers play a vital role in Restorative Justice. By exploring and listening to the volunteers’ experience, this study expands an additional strand within the literature in terms of what makes Restorative Justice effective and the challenges that are faced from a volunteer perspective

The South Asian genome

Genetics of disease Microarrays Variant genotypes Population genetics Sequence alignment AllelesThe genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.Whole genome sequencing to discover genetic variants underlying type-2 diabetes, coronary heart disease and related phenotypes amongst Indian Asians. Imperial College Healthcare NHS Trust cBRC 2011-13 (JS Kooner [PI], JC Chambers)

Mathematical modelling of the HIF-1 mediated hypoxic response in tumours

Solid tumours frequently display areas of low oxygen concentration (hypoxia) due to their uncontrolled proliferation and the fact that the new blood vessels they develop are irregular and have poor blood flow. The capacity for a tumour to grow therefore crucially depends on its ability to adjust to hypoxic conditions. It is frequently observed that the hypoxia response pathways, such as angiogenesis (formation of new blood vessels) and glycolysis (use of glucose, rather than oxygen, metabolism) are adapted in tumour cells to allow for aggressive growth in hypoxic conditions. The response pathways are also often upregulated in normoxic conditions. The transcription factor Hypoxia-Inducible Factor 1 (HIF-1) has been found to control the expression of a battery of genes that are crucially involved in the hypoxic response, including key angiogenic growth factors and glycolytic enzymes. Intratumoural hypoxia and HIF-1 overexpression are both associated with poor patient prognosis. In this paper, we extend an ordinary differential equation (ODE) model by Kohn et al, Mol. Biol. of the Cell, 15:3042(2004)that measures HIF-1 mediated transcription activation as a function of oxygen concetration [1]. The model considers a core sub-system of elements from the HIF-1 regulatory network,and in so doing highlights the stabilisation pathway of the oxygen-regulated HIF-1alpha subunit. In normoxic conditions HIF-1alpha undergoes a post-translational modification known as hydroxylation which allows HIF-1alpha to be targeted for degradation. In hypoxic conditions, the hydroxylation reaction does not occur, leading to stabilisation of the HIF-1alpha protein, formation of the HIF-1 complex and activation of gene transcription. We extend the Kohn model by including mechanisms that may account for the rapid attenuation of the hypoxic response upon reoxygenation of cells, after a period of hypoxia. Our results show good qualitative agreement with experimentally obtained hypoxia dose-response curves by capturing all the important characteristics of the curve

Coronary heart disease in Indian Asians.

The Indian Asian population accounts for a fifth of all global deaths from coronary heart disease (CHD). CHD deaths on the Indian subcontinent have doubled since 1990, and are predicted to rise a further 50% by 2030. Reasons underlying the increased CHD mortality among Indian Asians remain unknown. Although conventional cardiovascular risk factors contribute to CHD in Indian Asians as in other populations, these do not account for their increased risk. Type-2 diabetes, insulin resistance and related metabolic disturbances are more prevalent amongst Indian Asians than Europeans, and have been proposed as major determinants of higher CHD risk among Indian Asians. However, this view is not supported by prospective data. Genome-wide association studies have not identified differences in allele frequencies or effect sizes in known loci to explain the increased CHD risk in Indian Asians. Limited knowledge of mechanisms underlying higher CHD risk amongst Indian Asians presents a major obstacle to reducing the burden of CHD in this population. Systems biology approaches such as genomics, epigenomics, metabolomics and transcriptomics, provide a non-biased approach for discovery of novel biomarkers and disease pathways underlying CHD. Incorporation of these omic approaches in prospective Indian Asian cohorts such as the London Life Sciences Population Study (LOLIPOP) provide an exciting opportunity for the identification of new risk factors underlying CHD in this high risk population

Polymorphisms in the WNK1 gene are asociated with blood pressure variation and urinary potassium excretion

WNK1 - a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control - is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron 1, demonstrated the strongest evidence for association with SBP, effect size 3.14 mmHg (95%CI:1.23–4.9), DBP 1.9 mmHg (95%CI:0.7–3.2) and hypertension, odds ratio (OR: 1.3 [95%CI: 1.0–1.7]).We genotyped this variant in six independent populations (n = 14,451) and replicated the association between rs765250 and SBP in a meta-analysis (p = 7×10−3, combined with BRIGHT data-set p = 2×10−4, n = 17,851). The associations of WNK1 with DBP and EH were not confirmed. Haplotype analysis revealed striking associations with hypertension and BP variation (global permutation p10 mmHg reduction) and risk for hypertension (OR<0.60). Our data indicates that multiple rare and common WNK1 variants contribute to BP variation and hypertension, and provide compelling evidence to initiate further genetic and functional studies to explore the role of WNK1 in BP regulation and EH

Application of statistical and functional methodologies for the investigation of genetic determinants of coronary heart disease biomarkers: lipoprotein lipase genotype and plasma triglycerides as an exemplar

Genome-wide association studies have proved very successful in identifying novel single-nucleotide polymorphisms (SNPs) associated with disease or traits, but the related, functional SNP is usually unknown. In this paper, we describe a methodology to locate and validate candidate functional SNPs using lipoprotein lipase (LPL), a gene previously associated with triglyceride levels, as an exemplar. Two thousand seven hundred and eighty-six healthy middle-aged men from the NPHSII UK prospective study (with up to six measures of plasma lipid levels) were genotyped for 20 LPL tagging (t)SNPs using Illumina Bead technology. Using model-selection procedures and haplotypes, we identified eight SNPs that consistently maximized the fit of the model to the phenotype. Fifteen SNPs in high linkage disequilibrium with these were identified, and functional assays were carried out on all 23 SNPs. Electrophoretic mobility shift assay (EMSA) was used to identify SNPs that had the potential to alter DNA–protein interactions, reducing the number to eight possible candidate SNPs. These were examined for ability to alter expression using a luciferase reporter assay, and two regulatory SNPs, showing genotype differences, rs327 and rs3289, were identified. Finally, multiplexed-competitor-EMSA (MC-EMSA) and supershift EMSA identified FOXA2 to rs327T, and CREB-binding protein (CBP) and CCAAT displacement protein (CDP) to rs3289C as the factors responsible for transcription binding. We have identified two novel candidate functional SNPs in LPL and presented a procedure aimed to efficiently detect SNPs potentially causal to genetic association. We believe that this methodology could be successfully applied to future re-sequencing data

Management of Acute Coronary Syndromes During the Coronavirus Disease 2019 Pandemic: Deviations from Guidelines and Pragmatic Considerations for Patients and Healthcare Workers

Coronavirus disease 2019 (COVID-19) is forcing cardiology departments to rapidly adapt existing clinical guidelines to a new reality and this is especially the case for acute coronary syndrome pathways. In this focused review, the authors discuss how COVID-19 is affecting acute cardiology care and propose pragmatic guideline modifications for the diagnosis and management of acute coronary syndrome patients, particularly around the appropriateness of invasive strategies as well as length of hospital stay. The authors also discuss the use of personal protective equipment for healthcare workers in cardiology. Based on shared global experiences and growing peer-reviewed literature, it is possible to put in place modified acute coronary syndrome treatment pathways to offer safe pragmatic decisions to patients and staff

Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity